The thermic response to nutrients consists of an obligatory component, related to the energy cost of digestion and processing, and facultative thermogenesis, which is largely due to sympathetic stimulation. Insulin resistance leading to impaired glucose disposal may be the mechanism for blunted thermogenesis in obese people. It is now evident that prior exercise alters the thermic response to a meal, especially in the obese, but the underlying mechanisms are unknown. Exercise- induced improvement in the thermic effect of food in the obese may be due to increased glucose uptake and glycogen synthesis in muscle, secondary to increased insulin sensitivity. Skeletal muscle has been proposed to be an important site for the thermogenesis and also a likely site for insulin resistance. The beta-adrenergic component of thermogenesis may be specifically related to the beta2 adrenoreceptors which are the predominant type in muscle and are involved in carbohydrate metabolism. The proposed experiments will investigate: (1) the independent relationships of obesity and insulin sensitivity to thermogenesis; (2) characteristics of the effect of exercise on thermogenesis; (3) the role of beta1 and beta2 adrenergic receptors in thermogenesis; and (4) the quantitative relationships among exercise-induced changes in thermogenesis, glucose uptake and storage, and beta-adrenergically mediated sympathetic stimulation. Experiment 1 will compare the thermic effect of a 720 kcal mixed meal, measured by indirect calorimetry, in 2 groups of 10 lean (<18% fat), and 2 groups of 10 obese (>28% fat) men aged 25-45, who are matched at low and high levels of insulin sensitivity. Experiments 2&3 will compare in similar groups of 10 lean and 10 obese men; the thermic effect of food after 2 models of exercise which elicit the same V02, but differ in relative intensity, lactate and catecholamine responses, and the thermic effect food immediately after and the day after a bout of exercise. In Experiment 4, energy expenditure, and glucose disposal will be determined in 10 lean and 10 obese men during glucose clamp studies at rest and immediately post-exercise with no drug, with nonselective beta- blockade (propranolol), and with beta1-selective adrenergic blockade (metoprolol). In experiment 5, the thermic effect of food will be measured in 10 lean and 10 obese men at rest and post-exercise, with no drug, with metoprolol and with propranolol. In all experiments the lean and obese groups will be matched with regard to age, lean body mass, aerobic capacity, and normal glucose tolerance. These data will be used to clarify the association between obesity and impaired thermogenesis, independent of obesity-related insulin resistance, and to quantify and compare in lean and obese men: (1) the impact of exercise intensity on post-exercise thermogenesis; (2) the duration of the exercise effect; (3) the extent to which exercise-induced changes in thermogenesis are related to changes in insulin-stimulated glucose disposal; and (4) the degree to which nonselective- and beta1-selective adrenergic-blockade reduce thermogenesis (greater inhibition by propranolol will be evidence of beta2-adrenergic involvement). Information about the regulation of thermogenesis and mechanisms by which acute exercise may improve defects in glucose and energy metabolism in the obese will shed light on underlying metabolic abnormalities in obesity which in the long-run may lead to more effective treatment strategies.